Nucleic acids have been shown to have beneficial cosmetic and therapeutic effects on the skin. In experimental models, nucleic acids, such as cDNA coding for keratinocyte growth factor-1 (KGF-1) have been shown to improve wound healing (Lin et al., 2006, Wound Repair Regen., 14:618). Similarly, nucleic acid coding for interferon gamma have been shown to stimulate interferon production which inhibits collagen synthesis in the skin and has the potential to treat scleroderma, a tissue connective disease (Badea et al., 2005, J. Gene Med., 7:1200). In experimental models, siRNA targeting genes that code for the production of keratin in the skin were shown to inhibit these genes and have the potential to be used to treat the skin disorder pachyonychia congenita (Hickerson et al., 2006, Ann. N.Y. Acad. Sci., 1082:56).
However, a problem in achieving the potential cosmetic and therapeutic effects of these nucleic acids in humans has been the transdermal delivery of these molecules across the outer skin layer of the skin (i.e., stratum corneum) to the site of biological action, such as the epidermis and dermis, deeper underlying tissue, and/or remote sites within the body (Choi et al., In: Percutaneous Absorption, 4th Ed., Bronaugh and Maibach, ed., Taylor & Francis, Boca Raton, Fla., 2005). The stratum corneum is an effective physical barrier that prevents transdermal penetration of molecules such as nucleic acids. Skin enzymes can also act to destroy the nucleic acids through enzymatic degradation (Choi et al., supra).
Attempts have been made to chemically modify nucleic acids to prevent such degradation, but such modification typically impairs the biological activity of the agent and/or induces unfavorable immune system reactions. Chemical modifications are also disadvantageous because they are expensive and time-consuming.
Some methods have been used to attempt to improve transdermal penetration of nucleic acids, including tape-stripping the outer layer of the skin, electroporation or iontophoresis of the skin, use of semi-solid formulations (e.g., creams, etc.), chemical penetration enhancers which degrade the stratum corneum, and/or nonionic liposomes (Choi et al., supra). Each of methods has one or more disadvantages, such as damaging the outer layer of the skin (which can be painful and irritating to the patient), having a complexity of treatment that deters use by a physician and/or patients, increasing the complexity and related cost of manufacture, and/or potentially impairing the biological activity of the nucleic acids.
Thus, there is a need in the art for methods of transdermal delivery of nucleic acids (e.g., polynucleotides and nucleic acid residues) that are simple to use, that are cost-efficient, that do not damage the outer layer of the skin, that protect against enzymatic degradation without inducing immune reactions, that do not impair the biological activity of the nucleic acid to be delivered, and/or that may enhance delivery to the site of biological action in the target tissue.